Smoking of cannabinoid-enhanced "spices" is an emerging substance abuse problem. Although JWH-018 and other indole-derived cannabinoids that have been identified in Spice products produce marijuana-like intoxication, they are structurally distinct from cannabinoids contained in the cannabis plant;hence, in many states, they are not currently illegal and are readily available over the internet and in headshops. Indole-derived cannabinoids were originally developed as research tools to investigate the nature of cannabinoid receptors;however, very little is known about their pharmacology, particularly their behavioral effects, as only a small sample of the over 200 compounds in the JWH series have been tested in preclinical in vivo models. The proposed research will synthesize and evaluate JWH-018 and related indole-derived cannabinoids in rodent models that have been used to investigate the abuse properties of cannabinoids. Emphasis will be placed on determination of the extent to which the in vivo pharmacological profile of this class of cannabinoids differs from that of ?9-tetrahydrocannabinol, the primary psychoactive substituent of the marijuana plant. Further, use of male and female rodents will allow examination of possible sex differences in the effects of these cannabinoids. Results of the studies proposed here will increase knowledge of the behavioral effects of these abused cannabinoids in both sexes, thereby providing a scientific basis for evaluation of potential health concerns associated with acute and repeated use of the compounds, including their physical dependence liability. PUBLIC HEALTH RELEVANCE: Herbal blends ("Spice") containing synthetic cannabinoids, marketed over the internet as "incense," are being smoked as "legal marijuana" by drug abusers wanting to become intoxicated. Although most users report that these compounds produce marijuana-like effects, results of the handful of preclinical in vivo studies that have been completed with this class of cannabinoids have revealed differences, as well as similarities, with ?9-tetrahydrocannabinol, the primary psychoactive ingredient of marijuana. To determine the extent to which the behavioral effects of these synthetic indole-derived cannabinoids are distinct from those of ?9-tetrahydrocannabinol, the proposed research will examine the effects of selected synthetic cannabinoids that have been identified in "Spice" in rodent models of cannabinoid dependence.